tbuckley/cabot-search huggingface dataset:
Safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of AZD2936, a bispecific antibody targeting PD-1 and TIGIT, in checkpoint inhibitor (CPI)-experienced advanced/metastatic non-small-cell lung cancer (NSCLC): First report of ARTEMIDE-01.
Authors: Kristoffer Staal Rohrberg, Mariana Brandão, Eduardo Castanon Alvarez, Enriqueta Felip, Eelke Hiddo Gort, T.Jeroen Jeroen Nicolaas Hiltermann, Hiroki Izumi, Dong-Wan Kim, Sang-We Kim, Luis G. Paz-Ares, Benjamin J. Solomon, Laurie Steinbusch, Els Wauters, Tatsuya Yoshida, Huifang Chen, Andrew Goldwin, Yu Jiang, Ikbel Achour, Moritz Wolfgang Drachsler, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2023)

9050 Background: PD-1 and TIGIT are implicated in cancer-related T cell immunosuppression. AZD2936 is a bispecific, humanized IgG1 (triple-mutated to minimize Fc effector function) targeting PD-1 and TIGIT. It has demonstrated encouraging activity compared to both anti-PD-1 and anti-PD-1/-TIGIT combinations in murine models. We report data from dose escalation (Part A) and an expansion cohort (Part B) of the first-in-human study ARTEMIDE-01 (NCT04995523). Methods: This open-label, multicenter study enrolled pts with advanced NSCLC who had prior CPI treatment and a PD-L1 tumor proportion score ≥1%. Part A evaluated doses of 70–1500 mg IV Q3W; Part B evaluated the recommended phase 2 dose (RP2D). Primary endpoints included safety, tolerability, dose-limiting toxicities (DLTs) and preliminary efficacy. Secondary endpoints included PK and PD, defined as percentage PD-1 and TIGIT receptor occupancy (RO). Results: As of Dec 5, 2022, 80 pts were enrolled (Part A, n=48; Part B, n=32). Pts were 62.5% male, median age 63.5 years; 72.5% had adenocarcinoma, 23.8% had squamous cell carcinoma; 96.3% had metastatic disease; and 22.5% had brain metastases. They had a median of 2 prior regimens. Median duration of therapy was 11 wks. AZD2936 was well tolerated with no DLTs. In total, 46.3% of pts had treatment-related adverse events (TRAEs), all grade 1–3; the most common were pruritus, rash and lipase increased (6.3% each). Serious TRAEs occurred in 3 pts (3.8%): immune system disorder, acute hepatitis and fatigue (n=1 each). AZD2936 systemic exposure increased in a near dose-proportional manner. Doses of ≥210 mg achieved ~90% PD-1 and TIGIT RO in peripheral T cells. The RP2D was determined to be 750 mg Q3W based on safety, preliminary efficacy, PK/PD and modeling analysis predicting intratumoral RO. Among 76 evaluable pts, 3 had a partial response and 30 had stable disease (Table). Time to response was 1.9–4.0 mos and duration of response was 2.1–6.4 mos. Conclusions: In this interim analysis, AZD2936 showed an acceptable safety profile and preliminary antitumor activity in pts with advanced/metastatic NSCLC previously treated with standard therapy including CPIs. Further exploration of AZD2936 in CPI-naïve NSCLC pts, including a randomized dose optimization cohort is ongoing. Clinical trial information: NCT04995523 . [Table: see text]
A phase III study of lurbinectedin alone or in combination with irinotecan vs investigator's choice (topotecan or irinotecan) in patients with relapsed small cell lung cancer (SCLC; LAGOON trial).
Authors: Benjamin Besse, Luis G. Paz-Ares, Solange Peters, Federico Cappuzzo, Martin Reck, Antonio Calles, Raffaele Califano, Jose Antonio Lopez-Vilariño, Susie Veramendi, Carmen Maria Kahatt, Ali Hassan Zeaiter, Jacob Sands
Journal: Journal of Clinical Oncology (2023)

TPS8613 Background: Lurbinectedin is a novel synthetic chemical entity that acts as an inhibitor of oncogenic transcription and is active in tumors addicted to transcription. A phase II Basket trial (NCT02454972) in patients with small cell lung cancer (SCLC) treated with lurbinectedin in the second-line setting showed overall response rate (ORR) of 35.2% and median duration of response (DoR) of 5.3 months, with durable responses (43.0% ≥ 6 months). Based on these results, lurbinectedin was granted accelerated approval by the US FDA. An ongoing phase I/II trial (NCT02611024) is evaluating the lurbinectedin/irinotecan combination. Preliminary results showed ORR of 62% and median DoR of 5.7 months (2020 World Conference on Lung Cancer) warranting expansion to 100 patients. These results have supported the conduction of a phase III trial (LAGOON - NCT05153239). Methods: LAGOON is a randomized phase III clinical trial evaluating two experimental arms (lurbinectedin alone, 3.2 mg/m 2 D1 q3wk, or lurbinectedin 2 mg/m 2 D1 plus irinotecan D1, D8 q3wk) versus Investigator’s Choice (topotecan D1-5 q3wk or irinotecan D1 q3wk according to label) as control arm in relapsed SCLC patients. Approximately 705 patients will be enrolled. Central randomization will be implemented (1:1:1 ratio). Stratification will be done according to chemotherapy-free interval (CTFI) after first line (sensitive vs. resistant); prior anti-PD-(L)1; baseline central nervous system (CNS) involvement; lactate dehydrogenase value, and Investigator’s preference for the Control Arm. Main inclusion criteria include age ≥ 18 years, confirmed SCLC diagnosis, one prior line of platinum-containing chemotherapy with/without anti-PD-(L)1, and CTFI ≥ 30 days. Patients with CNS metastases can participate if pretreated and radiologically stable for at least 4 weeks. Main exclusion criteria include platinum-naïve patients, patients pretreated with more than one prior chemotherapy regimen (including platinum re-challenge), and prior treatment with lurbinectedin, trabectedin, PM14, or topoisomerase I inhibitors. An Independent Data Monitoring Committee will oversee the conduct of the study. An Independent Review Committee will provide the patient’s response at each tumor assessment endpoint to determine the best patient’s response and the date of objective response or progression/censoring according to RECIST v.1.1. Clinical trial information: NCT05153239 .
Validation of the distress thermometer score in a geriatric oncology population.
Authors: Charlotte Zuber, Kristine Swartz, Andrew E. Chapman, Lora Rhodes, Ting Ting Zhan, Kuang-Yi Wen
Journal: Journal of Clinical Oncology (2023)

e24030 Background: The geriatric oncology population is uniquely vulnerable to increased levels of psychological distress due to age related challenges such as social isolation, change in lifestyle, and comorbid conditions. In the general population, higher levels of psychological distress have been shown to impact treatment course, quality of life, and survival. The NCCN Distress Thermometer (DT) is a validated fast and effective screening tool for psychological distress, with a cutoff score of 4 yielding optimal sensitivity and specificity in a general cancer population. However, the best cutoff for detecting psychological morbidity in older cancer patients is unclear. In this study, we aim to compare the sensitivity and specificity of various cutoff values for the Distress Thermometer score to predict Geriatric Depression Scale (GDS) score. Methods: Data is derived from 242 geriatric oncology patients from the Senior Adult Oncology Center at Jefferson Health. Using a cutoff of 5 for the GDS as the clinical standard guideline, we use receiver operating characteristic (ROC) curve analysis of the univariable logistic regression model to predict clinical depression. Results: A cutoff DT score of 3.5 was found to be most sensitive and specific (0.66,0.68) for predicting clinical depression (Area Under the ROC Curve (AUC) = 0.70). Multivariable logistic regression including age improved the predictive ability of the DT score to an AUC of 0.75. Conclusions: The increase in AUC with the addition of age indicates the potential use of a composite value of age and DT score to best determine at-risk patients in a clinical setting. While these results indicate the utility of the Distress Thermometer as an effective screening tool in the geriatric oncology population, our findings also suggest that a lower threshold score is advised for clinicians who are hoping to identify older cancer patients who are distressed. Patients who meet the threshold criteria would then be assessed further for triage into appropriate levels of geriatric supportive services.
The impact of food insecurity on county-level colorectal cancer screening rates.
Authors: Mohammad Ali Syed Jafri, Alina Ashraf, Zorays Moazzam, Sara Ashraf
Journal: Journal of Clinical Oncology (2023)

e22519 Background: Colorectal cancer screening has been associated with a marked reduction in cancer- related mortality, and the achievement of screening targets has been identified as a national objective by the Healthy People 2030 initiative. Although various social determinants of health (SDoH) have been demonstrated to impact healthcare access, the association between food insecurity (FI) and colorectal screening rates (CSR) remains unexplored. As such, we sought to assess the impact of FI on county-level colorectal screening rates (CSR). Methods: Data on county-level colorectal cancer screening and food insecurity rates in 2018 were extracted from the Centers for Disease Control (CDC) PLACES and County Health Rankings &amp;amp; Roadmaps databases, respectively. Notably, FI and CSR were categorized as low (lowest quartile), intermediate (middle two quartiles) and high (highest quartile). Multivariable logistic regression analyses were used to evaluate the association between FI and CSR. Results: Among 3,106 counties, the median CSR was 62.1% (IQR 58.9%–65.2%) and ranged from 39.8% (Kusilvak, Alaska) to 74.4% (Newport, Rhode Island). A majority of counties were urban (Metropolitan: n = 790, 25.4% vs. Urban: n = 1,671, 53.8% vs. Rural: n = 645, 20.8%). Overall, a fourth of counties had high screening rates (Low CSR : n = 788, 25.4% vs. Intermediate CSR : n = 1,545, 49.7% vs. High CSR : n = 773, 24.9%). Similarly, 25.0% of counties demonstrated high FI (Low FI : n = 777, 25.0% vs. Intermediate FI : n = 1,552, 50.0% vs. High FI: n = 777, 25.0%). Notably, counties with increasing FI were markedly less likely to have High CSR (Low FI : n = 353, 45.4% vs. Intermediate FI: n = 370, 23.8% vs. High FI: n = 50, 6.4%)(p&amp;lt;0.001). After adjusting for county-level rurality, population-to-primary care physician ratio, household income, unemployment, race/ethnicity, education and uninsurance, intermediate and high FI was associated with an incrementally lower likelihood of having High CSR compared with low FI counties (ref: Low FI ; Intermediate FI : OR 0.61, 95%CI 0.47–0.80; High FI : OR 0.31, 95%CI 0.20–0.50). Conclusions: Increasing county-level FI was independently associated with markedly lower colorectal cancer screening rates, indicating that FI may play a key role in driving disparities in access to cancer care. As such, policies targeted at vulnerable communities characterized by high food insecurity and social deprivation are critically needed to ensure equitable access to preventive cancer care measures such as colorectal cancer screening.
The impact on hospice quality after initiation of an internal palliative care program by a community oncology practice.
Authors: Amy Foster, James L. Khatcheressian, Heather Lineberry, Shonda Clements, Shehnaz Pancholi, Karna Sheth
Journal: Journal of Clinical Oncology (2023)

e18720 Background: Virginia Cancer Institute (VCI) participated in the Oncology Care Model (OCM) with an aim to improve cancer care quality. As part of OCM, VCI started a palliative care program (PC) in 2016 by partnering with a local palliative care provider. In September 2020, VCI overhauled PC moving away from outside provider (OPC) and created an internal program (IPC). Both programs managed care from VCI oncologist referrals to PC until patient’s hospice start or practice discharge. This study describes the methods or changes from OPC to IPC and the resulting difference in hospice quality measure performance. Methods: Under OPC, services were provided half-day per week in office from a PC nurse practitioner (NP). IPC changed to a PC NP employed by VCI who provided services 5 days per week with office, hospital and telemedicine options. IPC added multiple PC education, communication touchpoints with oncologists and practice staff. IPC provided reminders to VCI physician teams about the availability of in-house PC services and the benefits of early engagement. Along with the oncologists, IPC continued goals of care discussions with patients and family to ensure patients’ desires and needs were met. OPC hospice referrals from PC went to a single hospice group. IPC added a network of multiple hospice groups. Retrospective claims review of OCM performance periods (PP) 1-8 (Jul 2016 – Dec 2020) for OPC and OCM PP 9-10 (Jul 2020 – Dec 2021) for IPC was performed and excluded patients with incomplete hospice claims. Primary endpoint was difference between OPC and IPC in OCM-3 quality: proportion of OCM patients who died during their episode with 3 or more days hospice immediately prior to death. Secondary endpoint was the difference in proportions of OPC and IPC with any hospice length of stay. Z-test between 2 proportions was used to calculate significance. Results: There were 871 and 197 OCM-3 eligible patients reviewed from OPC and IPC respectively. OCM-3 quality performance was 48.1% OPC and 62.4% IPC, p &lt; 0.01. Any hospice performance was 65.8% OPC and 78.7% IPC, p &lt; 0.01. The OCM-3 goal throughout for maximum quality score was 60%. Performance improvement started in the first IPC period (PP9) and was greater in the second IPC period (PP10). Conclusions: Results showed a significant improvement in OCM performance measures between OPC and IPC over a short period of 10 months. After IPC, practice met the OCM-3 goal. The data is limited to latest available OCM reconciliation claims and may be refreshed when additional OCM data is released. Although specific cause and effect was not assessed, the authors attribute quality improvement to the implementation of an internal, full-time PC NP. This expanded PC access for patients and increased communication between patients and providers. We believe that, as a result, the quality of care delivery improved.
Identification and characterization of karyopherin a-2, a nuclear export protein in lung adenocarcinoma.
Authors: Seoree Kim, Heejin Lee, Jung-Sook Yoon, Joon Won Jeong, Ji Hyun Lee, Sang Hoon Chun, Hye Sung Won, Soon Auck Hong, Keunsoo Kang, Young-Ho Ahn, Yoon Ho Ko, Hojung An
Journal: Journal of Clinical Oncology (2023)

e21025 Background: It is emerging that the Karyopherin a-2 (KPNA2), a nucleocytoplasmic transport protein, regulates the nuclear import of macromolecules and contributes to carcinogenesis and changes in cellular phenotype. In particular, it can be a poor prognostic marker by causing aberrant subcellular localization of DNA damage response proteins or OCT4-c MYC pathway molecules depending on the type of carcinoma and inducing anticancer resistance. In some carcinomas, an association with the p53 oncogenic pathway has been reported, showing good prognostic values. We aimed to investigate the clinical significance and metabolic pathway of stable cancer associated fibroblast (CAF) and cancer cells for KPNA2. Methods: We retrospectively analyzed the data extracted from EMR for NSCLC patients receiving curative surgical resection in Uijeongbu and Bucheon St. Mary’s Hospitals (n = 165). Immunohistochemistry staining was performed on the tumor microarray samples using antibodies against KPNA2. The functional assay and gene silencing was conducted. Results: Based on the TMA staining, mean KPNA2 score was 36.5 [0-240] and median value was 10. The clinical and pathological information of the experimental group is as follows. Table 1. Scatter plots and correlation between KPNA2 expression levels and tumor invasiveness markers reveals that high KPNA2 expressor was related to lymphatic invasion (p = 0.00782), advanced stage (p = 0.0202) and current smoker (p = 0.0074). KPNA2 expression was higher in squamous cell carcinoma(SqCC) histotype than in adenocarcinoma (SqCC ratio (%), 13.5 vs 43.4 in Low exp vs High exp; p = 0.007). Patients with high expression of KPNA2 showed shorter survival than other patients (median OS (months), 72.8 vs 42.2, P &lt; 0.0001; median RFS (months), 72.8 vs 32.1, P &lt; 0.0011) and relevant to high recurrence (recurrence rate (%), 24.7 vs 44.7, p = 0.007). Further, high KPNA2 expression was associated with poor survival outcomes. To test the effect of KPNA2 on cancer cell invasion, we knocked down Kpna2 via shRNA. Spheroids composed of H1299, Calu-6, A549, HCC827 lung cancer cells with either Kpna2-overexpression or Kpna2-knockdown, and spheroid invasion was then monitored for two days. Eminently, the 3-D invasion of spheroids was suppressed via Kpna2 knockdown. In addition, Kpna2-overexpressing cells promoted cancer invasion to a greater extent than control. Conclusions: In conclusion, our results suggest that KPNA2 protein expression has a poor prognostic association, revealed by its association with survival outcome or invasiveness markers. Its clinical significance as an oncogenic target molecule is emerging, and further evaluation using an organoid model is in progress.
Clinical outcomes for immunotherapy beyond progression in patients with advanced non-small cell lung cancer.
Authors: Wenxiao Jia, Min Wang, Hui Zhu, Gang Wu
Journal: Journal of Clinical Oncology (2023)

e21222 Background: No definite conclusion has yet to be reached for immunotherapy beyond progression(IBP)as the second-line treatment for advanced NSCLC patients with negative driver genes. Therefore, a retrospective study was conducted to evaluate the efficacy of IBP in this population and investigated whether the cycles, best response and progressive mode of first-line immunotherapy could affect the results. Methods: The clinical data of patients with advanced NSCLC whose response was evaluated as progressive disease (PD) after receiving a PD-1/PD-L1 inhibitors as first-line therapy were retrospectively collected and the patients were assigned to the IBP and non-IBP groups. The overall survival (OS), progression-free survival (PFS) were evaluated between the two groups. The survival effects of cycles, best response and progressive mode of first-line immunotherapy were also evaluated. Results: Between January 2019 and January 2022, a total of 121 patients was evaluated as PD after first-line immunotherapy in our institution; 53 (43.8%) patients were included in the IBP group and 68 (56.2%) patients were included in the non-IBP group. The OS and PFS were no significantly different between the two groups. Further analysis revealed the OS was prolonged with the prolongation of first-line medication cycle. The median OS was 15.4m (15.4 vs 10.8 p= 0.029), 16.1m (16.1 vs 10.8 p= 0.021), 16.3m (16.3 vs 10.9 p= 0.015) for patients with ≥4, ≥6, ≥8 cycles in first-line immunotherapy, respectively. The advantages of OS and PFS were also seen in the subgroup of PR (best response) and local progression of first-line immunotherapy. Conclusions: The clinical outcomes of IBP were similar to those of non-IBP in patients with PD after first-line immnuotherapy in advanced NSCLC. But more cycles, PR as best response and local progression in first-line was benefit.
Early introduction to clinical radiation oncology through a self-directed competency-based medical student curriculum.
Authors: Cheryl Claunch, Shraddha Dalwadi, Jarey Wang, Michelle Suzanne Ludwig
Journal: Journal of Clinical Oncology (2023)

11038 Background: Specialty training is not traditionally incorporated into standard medical education and there is a deficiency in exposure to Radiation Oncology for “last minute” interested candidates, particularly from underrepresented backgrounds. Therefore, we implemented MERAO-200, an introductory 2-week in-person and virtual medical education curriculum without clinical prerequisites to facilitate early introduction to the field of Radiation Oncology and report its effect on student comfort and familiarity with radiation planning and contouring. Methods: Clinical students were enrolled in a 2-week elective without clinical prerequisites that integrated both clinical activities and self-directed learning through virtual contouring modules. The virtual curriculum was designed around three modules available on EduCase. A survey was conducted after completion of the modules that solicited self-identifying information and to assess their efficacy in increasing understanding of basic contouring skills. Paired t-tests were used to compare pre- and post-elective assessment results. Results: Twenty-three total students have completed MERAO-200 from Fall 2020 to Spring 2023. Of those, 15 submitted the survey. Eight (53%) students did not answer self-identifying information such as gender, race, ethnicity, or country of origin. Four (27%) students identified as Asian and 3 (20%) as white. No students identified as Hispanic, Latino or Spanish origin. Seven (46%) students identified as having USA as country of origin. Seven (47%) students reported interest in radiation oncology, medical oncology or surgical oncology. Three (20%) students were MS2, 7 (47%) were MS3, and 5 (33%) were MS4. Overall, there was a significant increase in comfort level using radiation planning software (p = 1.1e-4) as well as ability to find relevant contouring references (p = 4.2e-5). Knowledge of the anatomy and contouring principles also improved for the three modules: eye and brain (p = 2.8e-7), high grade glioma (3.2e-6), and head and neck nodal stations (4.5e-6). CNS module difficulty on a scale of 1-10 had a median difficulty score of 7 (range 3-8) and head and neck module difficulty was a median of 7 (range 3-10). Conclusions: Implementation of MERAO-200 improved medical student exposure to the field of Radiation Oncology and improved medical student comfort and familiarity with radiation planning and across all disease sites covered. More outreach work needs to be done to facilitate inclusion of minority student populations and students from underrepresented backgrounds. Early introduction at the medical student level could be a pathway to improve disparity in the field of Radiation Oncology.